Home About us Contact
|
Home About us Contact | ||
|
|
||
Genotype Differences (genotype + difference)
Selected AbstractsInterferon-, treatment in children and young adults with chronic hepatitis B: a long-term follow-up study in TaiwanLIVER INTERNATIONAL, Issue 9 2008Hong-Yuan Hsu Abstract Background/Aims: The short- and long-term benefits of interferon (IFN)-, therapy in young patients with chronic hepatitis B (CHB) acquiring infection perinatally or during early childhood have been questioned. Methods: Twenty-one Taiwanese hepatitis B envelope antigen (HBeAg)-positive CHB patients aged 1.8,21.8 years (median 14.0 years) with alanine aminotransferase (ALT)>80 IU/L at entry were enrolled for IFN-, therapy. They received IFN-, therapy with a dose of 3 MU/m2/day three times a week for 24 weeks. A control group included untreated 21 CHB patients closely matched for gender, age, duration of ALT >80 IU/L and HBeAg status. All 42 patients were prospectively followed for 6.5,12.5 years after the end of therapy. Results: The cumulative rate of virological response [anti-HBe seroconversion and serum hepatitis B virus (HBV)-DNA <105 copies/ml] was not different between the IFN-treated patients and control patients at 1 year (41 vs 44%) and at 6 years (88 vs 89%) after stopping treatment. Serum hepatitis B surface antigen loss occurred in two (9.5%) treated patients and in one (4.8%) control patient. Patients with a successful treatment response (anti-HBe seroconversion, HBV-DNA <102 copies/ml and ALT normalization at 1 year after stopping treatment) were younger than those without a successful response (P=0.03). A lower pretreatment serum HBV-DNA level (<2 × 108 copies/ml) is not only a significant factor to predict successful treatment response (P=0.008) but also has a beneficial effect on the long-term cumulative rate of virological response in IFN-treated patients (P=0.021), but not in control patients. Genotype difference or emergence of a precore stop codon mutant before treatment was not predictive for HBeAg clearance. Conclusion: For young CHB patients in Taiwan with infection occurring perinatally or in early childhood, the real advantage of IFN-, therapy was not observed. IFN-, therapy showed a beneficial effect on short- and long-term virological outcomes only in those with a lower pretreatment serum HBV-DNA level. [source] Genotype differences in cognitive functioning in Noonan syndromeGENES, BRAIN AND BEHAVIOR, Issue 3 2009E. I. Pierpont Noonan syndrome (NS) is an autosomal-dominant genetic disorder associated with highly variable features, including heart disease, short stature, minor facial anomalies and learning disabilities. Recent gene discoveries have laid the groundwork for exploring whether variability in the NS phenotype is related to differences at the genetic level. In this study, we examine the influence of both genotype and nongenotypic factors on cognitive functioning. Data are presented from 65 individuals with NS (ages 4,18) who were evaluated using standardized measures of intellectual functioning. The cohort included 33 individuals with PTPN11 mutations, 6 individuals with SOS1 mutations, 1 individual with a BRAF mutation and 25 participants with negative, incomplete or no genetic testing. Results indicate that genotype differences may account for some of the variation in cognitive ability in NS. Whereas cognitive impairments were common among individuals with PTPN11 mutations and those with unknown mutations, all of the individuals with SOS1 mutations exhibited verbal and nonverbal cognitive skills in the average range or higher. Participants with N308D and N308S mutations in PTPN11 also showed no (or mild) cognitive delays. Additional influences such as hearing loss, motor dexterity and parental education levels accounted for significant variability in cognitive outcomes. Severity of cardiac disease was not related to cognitive functioning. Our results suggest that some NS-causing mutations have a more marked impact on cognitive skills than others. [source] The Influence of an Insulin-Like Growth Factor I Gene Promoter Polymorphism on Hip Bone Geometry and the Risk of Nonvertebral Fracture in the Elderly: The Rotterdam Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2004Fernando Rivadeneira Abstract The absence of the wildtype allele of a promoter polymorphism of the IGF-I gene is associated with increased risk (1.5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways. Introduction: Previously, we found a CA-repeat promoter polymorphism in the insulin-like growth factor I (IGF-I) gene associated with IGF-I levels and BMD in postmenopausal women, but the relationship with fractures is unclear. In this large population-based study of elderly men and women, we examined the association between this IGF-I promoter polymorphism with parameters of bone geometry and the occurrence of fractures. Material and Methods: Within the Rotterdam Study, a prospective population-based cohort, the IGF-I polymorphism was analyzed in relation to incident nonvertebral fractures in 2799 men and 4212 women followed on average for 8.6 years. Furthermore, we estimated structural parameters of hip bone geometry indirectly from DXA outputs of the femoral neck in 2372 men and 3114 women. We studied neck width, cortical thickness, and the cortical buckling ratio and the section modulus as indexes of bone stability and bending strength. Results: Women heterozygotes and noncarriers of the allele had, respectively, 1.2 (95% CI, 1.0-1.5) and 1.5 (95% CI, 1.1-2.0) increased risk of having a fragility fracture at older age compared with homozygotes for the 192-bp allele (p trend = 0.0007). In men, fracture risk was not influenced by the polymorphism. Compared with homozygotes for the 192-bp allele, noncarrier males had ,1% narrower femoral necks and 2.2% lower section moduli (p trend < 0.05). Noncarrier females had 1.7% thinner cortices and 1.6% higher buckling ratios (p trend < 0.05) but no significant differences in femoral neck widths and section moduli. In women with low body mass index, genotype differences in bone strength (section modulus) and fracture risk were accentuated (p interaction = 0.05). The genotype-dependent differences in hip bone geometry did not fully explain the genotype-dependent differences in fracture risk. Conclusions: The CA-repeat promoter polymorphism in the IGF-I gene is associated with the risk for fragility fracture at old age in women and with bone structure in both genders. [source] Increase in Free Choice Oral Ethanol Self-Administration in Catechol- O -Methyltransferase Gene-Disrupted Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Anne Tammimäki Solutions containing ethanol or cocaine, or tap water were available ad libitum from drinking burettes for 4 weeks. Catechol- O -methyltransferase-deficient male mice consumed significantly more ethanol than their wild-type male littermates. In contrast, female mice did not show genotype differences in the consumption of ethanol solutions. During the cocaine experiment, male mice developed either a side preference or an aversion that obscured cocaine consumption. This pattern of drinking was not dependent on Comt genotype. In female mice, Comt genotype was not associated with cocaine consumption. In conclusion, disruption of Comt gene influenced ethanol consumption in a gender-dependent manner in mice, supporting the hypothesis that low catechol- O -methyltransferase activity is one of the predisposing factors for high alcohol consumption in males. [source] | ||||||||||